Revealing potential long non-coding RNA biomarkers in lung adenocarcinoma using long non-coding RNA-mediated competitive endogenous RNA network

T-G Zhu, X Xiao, Q Wei, M Yue, L-X Zhang

In our study, we aimed to reveal potential long non-coding RNAs (lncRNA) biomarkers in lung adenocarcinoma (LAD) using lncRNA-mediated competing endogenous RNAs (ceRNAs) network (LMCN). Competing lncRNA-mRNA interactions were identified using the hypergeometric test. Co-expression analysis for the competing lncRNA-mRNA interactions was implemented, and relying on the weight value >0.8, a highly competitive LMCN was further constructed. Degree distribution, betweenness and closeness for LMCN were carried out to analyze the network structure. Functional analyses of mRNAs in LMCN were carried out to further explore the biological functions of lncRNAs. Biclique algorithm was utilized to extract competing modules from the LMCN. Finally, we verified our findings in an independent sample set using qRT-PCR. Based on degrees >60, we identified 4 hubs, including DLEU2, SNHG12, HCP5, and LINC00472. Furthermore, 2 competing modules were identified, and LINC00472 in module 1 functioned as a hub in both LMCN and module. Functional implications of lncRNAs demonstrated that lncRNAs were related to histone modification, negative regulation of cell cycle, neuroactive ligand-receptor interaction, and regulation of actin cytoskeleton. qRT-PCR results demonstrated that lncRNAs LINC00472, and HCP5 were down-regulated in LAD tissues, while the expression level of SNHG12 was up-regulated in LAD tissues. Our study sheds novel light on the roles of lncRNA-related ceRNA network in LAD and facilitates the detection of potential lncRNA biomarkers for LAD diagnosis and treatment. Remarkably, in our study, LINC00472, HCP5, and SNHG12 might be potential biomarkers for LAD management.